The Geomorphosites in Lombardy

Lombardy is a region of Northern Italy with a territory whose structure includes, from the physical-geographical point of view, a very important portion of the Alps and the adjacent Po plain with a little part of the Northern Apennines. This situation is due to the complexity of the landscape with its great diversity of historical and human aspects, frequently studied and described, but also the same physical elements which are, owing to their interest, worthy of conservation as part of the cultural heritage. As in many other Italian regions and provinces, also in Lombardy the exigence of describing and making available sites and peculiarities of the landscape arose, together with the suggestion of specific naturalistic tours, by means of relative guidebooks, monographs and so on. The Authors of the present work (as a part of the national research programme on ‘Geosites and Italian Landscape’) made a census of geomorphosites in Lombardy in order to their improvement, conservation and availability, both on the tourist and the scientific level. From the operating point of view, because of the high heterogeneity of the Lombard physical landscapes, it has been necessary to differentiate three main areas: Alps, Po plain and Apennines. Then, owing to its didactic exemplariness, its rarity and its paleogeographic or evolutive evidence, the geomorphological sites having a specific value have been identified and described, and also typologically assembled. Till now more than 150 sites have been registered. Some of them are single geomorphosites and others correspond with their areal but significant distribution. Someone of them are moreover well known as tourist sites, but many others, instead, have not had such consideration, yet. With contribution of Stefania De Vit

The Geomorphosites in Lombardy

Lombardy is a region of Northern Italy with a territory whose structure includes, from the physical-geographical point of view, a very important portion of the Alps and the adjacent Po plain with a little part of the Northern Apennines. This situation is due to the complexity of the landscape with its great diversity of historical and human aspects, frequently studied and described, but also the same physical elements which are, owing to their interest, worthy of conservation as part of the cultural heritage. As in many other Italian regions and provinces, also in Lombardy the exigence of describing and making available sites and peculiarities of the landscape arose, together with the suggestion of specific naturalistic tours, by means of relative guidebooks, monographs and so on. The Authors of the present work (as a part of the national research programme on ‘Geosites and Italian Landscape’) made a census of geomorphosites in Lombardy in order to their improvement, conservation and availability, both on the tourist and the scientific level. From the operating point of view, because of the high heterogeneity of the Lombard physical landscapes, it has been necessary to differentiate three main areas: Alps, Po plain and Apennines. Then, owing to its didactic exemplariness, its rarity and its paleogeographic or evolutive evidence, the geomorphological sites having a specific value have been identified and described, and also typologically assembled. Till now more than 150 sites have been registered. Some of them are single geomorphosites and others correspond with their areal but significant distribution. Someone of them are moreover well known as tourist sites, but many others, instead, have not had such consideration, yet

A Functional Precision Oncology Approach to Identify Treatment Strategies for Myxofibrosarcoma Patients

In this era of precision medicine, numerous workflows for the targeting of high-recurrent mutations in common tumor types have been developed, leaving patients with rare diseases with few options. Here, we implement a functional precision oncology approach utilizing comprehensive genomic profiling in combination with high-throughput drug screening, to identify tumor-specific drug sensitivities for patients with rare tumor types such as myxofibrosarcoma. From a patient with a high-grade myxofibrosarcoma, who was enrolled in the Englander Institute for Precision Medicine (EIPM) program, we established patient-derived 3D sarco-spheres and xenograft models for functional testing. In the absence of a large cohort of clinically similar cases, high-throughput drug screening was performed on the patient-derived cells, and compared with two other myxofibrosarcoma lines and a benign fibroblast line to functionally identify tumor-specific drug sensitivities. The addition of functional drug sensitivity testing to complement genomic profiling identified multiple therapeutic options that were further validated in patient derived xenograft models. Genomic analyses detected the frequently known codeletion of the tumor suppressors CDKN2A/B together with the methylthioadenosine phosphorylase (MTAP) and a TP53 E286fs*50 mutation. High-throughput drug screening demonstrated tumor-specific sensitivity to compounds targeting the cell cycle. Based on genomic analysis and high-throughput drug screening, we show that targeting the cell cycle in these tumors is a powerful approach. IMPLICATIONS: This study demonstrates the potential of functional testing to aid clinical decision making for patients with rare or molecularly complex malignancies when combined with comprehensive genomic profiling

A Functional Precision Oncology Approach to Identify Treatment Strategies for Myxofibrosarcoma Patients.

In this era of precision medicine, numerous workflows for the targeting of high-recurrent mutations in common tumor types have been developed, leaving patients with rare diseases with few options. Here, we implement a functional precision oncology approach utilizing comprehensive genomic profiling in combination with high-throughput drug screening, to identify tumor-specific drug sensitivities for patients with rare tumor types such as myxofibrosarcoma. From a patient with a high-grade myxofibrosarcoma, who was enrolled in the Englander Institute for Precision Medicine (EIPM) program, we established patient-derived 3D sarco-spheres and xenograft models for functional testing. In the absence of a large cohort of clinically similar cases, high-throughput drug screening was performed on the patient-derived cells, and compared with two other myxofibrosarcoma lines and a benign fibroblast line to functionally identify tumor-specific drug sensitivities. The addition of functional drug sensitivity testing to complement genomic profiling identified multiple therapeutic options that were further validated in patient derived xenograft models. Genomic analyses detected the frequently known codeletion of the tumor suppressors CDKN2A/B together with the methylthioadenosine phosphorylase (MTAP) and a TP53 E286fs*50 mutation. High-throughput drug screening demonstrated tumor-specific sensitivity to compounds targeting the cell cycle. Based on genomic analysis and high-throughput drug screening, we show that targeting the cell cycle in these tumors is a powerful approach. IMPLICATIONS: This study demonstrates the potential of functional testing to aid clinical decision making for patients with rare or molecularly complex malignancies when combined with comprehensive genomic profiling

Effect of centre volume on pathological outcomes and postoperative complications after surgery for colorectal cancer: results of a multicentre national study

Background: The association between volume, complications and pathological outcomes is still under debate regarding colorectal cancer surgery. The aim of the study was to assess the association between centre volume and severe complications, mortality, less-than-radical oncologic surgery, and indications for neoadjuvant therapy.Methods: Retrospective analysis of 16,883 colorectal cancer cases from 80 centres (2018-2021). Outcomes: 30-day mortality; Clavien-Dindo grade >2 complications; removal of >= 12 lymph nodes; non-radical resection; neoadjuvant therapy. Quartiles of hospital volumes were classified as LOW, MEDIUM, HIGH, and VERY HIGH. Independent predictors, both overall and for rectal cancer, were evaluated using logistic regression including age, gender, AJCC stage and cancer site.Results: LOW-volume centres reported a higher rate of severe postoperative complications (OR 1.50, 95% c.i. 1.15-1.096, P = 0.003). The rate of >= 12 lymph nodes removed in LOW-volume (OR 0.68, 95% c.i. 0.56-0.85, P = 12 lymph nodes removed was lower in LOW-volume than in VERY HIGH-volume centres (OR 0.57, 95% c.i. 0.41-0.80, P = 0.001). A lower rate of neoadjuvant chemoradiation was associated with HIGH (OR 0.66, 95% c.i. 0.56-0.77, P < 0.001), MEDIUM (OR 0.75, 95% c.i. 0.60-0.92, P = 0.006), and LOW (OR 0.70, 95% c.i. 0.52-0.94, P = 0.019) volume centres (vs. VERY HIGH).Conclusion: Colorectal cancer surgery in low-volume centres is at higher risk of suboptimal management, poor postoperative outcomes, and less-than-adequate oncologic resections. Centralisation of rectal cancer cases should be taken into consideration to optimise the outcomes